Life starting – and evolving – in a test tube

A much-debated theory holds that 4 billion years ago, the primordial soup contained only the possibility of life. Then a molecule called RNA took a dramatic step into the future: It made a copy of itself.

Then the copy made a copy, and over the course of many millions of years, RNA begot DNA and proteins, all of which came together to form a cell, the smallest unit of life able to survive on its own.

Now, in an important advance supporting this theory, scientists at the Salk Institute for Biological Studies in La Jolla, California, have carried out a small but essential part of the story. In test tubes, they developed an RNA molecule that was able to make accurate copies of a different type of RNA.

The work, published in the journal Proceedings of the National Academy of Sciences, gets them closer to the grand goal of growing an RNA molecule that makes accurate copies of itself.

“Then it would be alive,” said Gerald Joyce, president of Salk and one of the authors of the new paper. “So, this is the road to how life can arise in a laboratory or, in principle, anywhere in the universe.”

The team remains a ways off from showing that this is how life on Earth truly began, but the scenario they tested probably mimics one of the earliest stirrings of evolution, a concept described by the English naturalist Charles Darwin more than 150 years ago.

“This is a stepping stone toward understanding how life evolved,” said Nikolaos Papastavrou, first author of the paper and a Salk post-doctoral fellow.

To reach this point, the scientists overcame perhaps the greatest barrier to the plausibility of the RNA World theory. Up to now, no RNA molecule in the lab had succeeded in making copies of another RNA that were both sufficiently accurate and functional.

An RNA molecule must make copies very close to the original to achieve the same delicate balance that governs Darwinian evolution in nature. If the copies change too much, the RNA’s abilities degenerate, like an image that fades as it is repeatedly copied and printed.

Though the copying has to be very good, it can’t be letter-perfect all the time. Without some room for mistakes, the RNA would be unable to adapt when its environment changed, as living creatures must do in the wild.

John Chaput, a professor of pharmaceutical sciences at the University of California at Irvine who did not participate in the study, called the crossing of that threshold by the Salk team “monumental” and “a little bit jaw-dropping”.

Although the experiments in the new paper took two years, it has taken Joyce and his colleagues closer to 10 years to set the stage, patiently raising generation upon generation of RNA molecules.

Should the scientists succeed in generating an RNA that can copy itself, evolution could then proceed largely on its own.

The RNA molecules could adapt as scientists changed the temperature or environment, or added new chemicals.

“Once evolution got going on Earth,” Joyce said, “look at all the amazing things it invented.”

“This is the road to how life can arise in a laboratory or, in principle, anywhere in the universe.”

Gerald Joyce, Salk Institute president